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The ZP domain is a conserved module for polymerization of extracellular proteins

Nature Cell Biology volume 4, pages 457–461 (2002)Cite this article

Abstract

Many eukaryotic extracellular proteins share a sequence of unknown function, called the zona pellucida (ZP) domain1. Among these proteins are the mammalian sperm receptors ZP2 and ZP3, non-mammalian egg coat proteins, Tamm-Horsfall protein (THP), glycoprotein-2 (GP-2), α- and β-tectorins, transforming growth factor (TGF)-β receptor III and endoglin, DMBT-1 (deletd in malignant brain tumour-1), NompA (no-mechanoreceptor-potential-A), Dumpy and cuticlin-1 (refs 1,2). Here, we report that the ZP domain of ZP2, ZP3 and THP is responsible for polymerization of these proteins into filaments of similar supramolecular structure. Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors1,2. Our results demonstrate that the C-terminal transmembrane domain and short cytoplasmic tail of ZP2 and ZP3 are not required for secretion, but are essential for assembly. Finally, we suggest a molecular basis for dominant human hearing disorders caused by point mutations within the ZP domain of α-tectorin3,4,5.

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Figure 1: Sequence features and predicted domain structure of ZP2, ZP3 and THP.
Figure 2: The ZP domains of ZP2 and ZP3 are essential for their assembly.
Figure 3: Filaments of THP-ZPD and mouse ZP share a similar supramolecular structure.
Figure 4: Mutations affecting assembly and secretion of ZP domain proteins.

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Acknowledgements

We thank F. Serafini-Cessi for advice on THP purification, W.G.M. Janssen for help with EM analysis of THP and J.E. Heuser for imaging of mouse ZP filaments. We are also grateful to R. De Santis for communicating results before publication and to F. Cotelli, M. Paterlini and V. Gusarova for discussion. Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resource Facility; the N-terminal sequence of THP-ZPD was determined at the HHMI/Columbia University Protein Chemistry Core Facility. L.J. is supported by a Human Frontier Science Program long-term fellowship. This research was supported in part by National Institutes of Health grant HD35105.

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  1. Luca Jovine and Huayu Qi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, 10029-6574, NY, USA

    Luca Jovine, Huayu Qi, Zev Williams, Eveline Litscher & Paul M. Wassarman

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  1. Luca Jovine
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Correspondence to Paul M. Wassarman.

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Jovine, L., Qi, H., Williams, Z. et al. The ZP domain is a conserved module for polymerization of extracellular proteins. Nat Cell Biol 4, 457–461 (2002). https://doi.org/10.1038/ncb802

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